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Method comparison of tumor markers assessed by LOCI™- and ECLIA-based technologies

  • Ramona C. Dolscheid-Pommerich EMAIL logo , Sarah Dolscheid , Lars Eichhorn , Berndt Zur , Stefan Holdenrieder and Birgit Stoffel-Wagner
Published/Copyright: January 31, 2017
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LaboratoriumsMedizin
From the journal LaboratoriumsMedizin Volume 41 Issue 1

Abstract

Background:

Since the introduction of luminescent oxygen channeling immunoassays (LOCI™)-based assays in the daily laboratory routine of tumor marker measurements, only a small number of method comparisons with established immunoassays have been published. We performed a method comparison between LOCI™-based tumor marker assays for Dimension™ VISTA and electrochemiluminiscent immunoassays (ECLIA) for Cobas™ e411, for α-fetoprotein (AFP), carcinoembryonic antigen (CEA), CA 125, CA 15-3, CA 19-9, prostate-specific antigen (PSA) and free PSA (fPSA).

Methods:

Tumor markers were assessed in 1088 sera from routine diagnostics on the Dimension™ VISTA 1500 and Cobas™ e411 analyzers.

Results:

Strong correlations were achieved for PSA (r=0.999), AFP (r=0.994) and CEA (r=0.993). Results were quite comparable as only minor slopes of 1.05 (PSA), 1.02 (AFP) and 0.94 (CEA), respectively, were found. However, correlations for CA 125 (r=0.976), CA 19-9 (r=0.960), fPSA (r=0.950) and CA 15-3 (r=0.940) were only moderate, and considerable slopes were observed for these markers with higher values for CA 19-9 (slope 1.50) and lower ones for CA 15-3 (0.76), fPSA (0.75) and CA 125 (0.64), for Dimension™ VISTA 1500.

Conclusions:

We found excellent correlations and comparable values for AFP, CEA and PSA, but only moderate correlations for fPSA, CA 125, CA 15-3 and CA 19-9. The slopes for CA 19-9, CA 15-3, fPSA and CA 125 have to be considered when analysis methods for tumor markers are changed.

Zusammenfassung

Hintergrund:

Seit der Einführung von LOCI™-assays in der Routinediagnostik wurden nur wenige Methodenvergleiche mit etablierten Immunoassays publiziert. Methodenvergleich von Tumormarkern AFP, CEA, CA125, CA 15-3, CA 19-9, PSA und freies PSA (fPSA) mittels LOCI™-assays für den Dimension™ VISTA und Cobas™ e411.

Methoden:

AFP, CEA, CA125, CA 15-3, CA 19-9, PSA und freies PSA (fPSA) wurden in 1088 Seren auf dem Dimension™ Vista 1500 und Cobas™ e411 bestimmt.

Ergebnisse:

Gute Korrelationen zeigten sich für PSA (r=0.999), AFP (r=0.994) und CEA (r=0.993) mit einer guten Vergleichbarkeit der Ergebnisse bei nur geringen Abweichungen von 1.05 (PSA), 1.02 (AFP) and 0.94 (CEA). Für CA125 (r=0.976), CA 19-9 (r=0.960), fPSA (r=0.950) und CA 15-3 (r=0.940) zeigten sich mäßige Korrelationen mit erheblichen Abweichungen und höheren Werten für den Dimension™ Vista 1500 für CA 19-9 (slope 1.50) und niedrigeren Werten für CA 15-3 (0.76), fPSA (0.75), and CA 125 (0.64).

Schlussfolgerung:

Für AFP, CEA und PSA zeigten sich hervorragende Korrelationen mit vergleichbaren Werten für beide Methoden, wohingegen fPSA, CA125, CA 15-3 und CA 19-9 nur mäßig korrelierten. Wenn Methoden zur Tumormarkerbestimmung umgestellt werden, müssen demnach die Abweichungen für CA 19-9, CA 15-3, fPSA und CA 125 beachtet werden.

Reviewed Publication:

Holdenrieder S.

Keywords: AFP; CA 15-3; CA 125; immunoassay; tumor marker
Schlüsselwörter:: AFP; CA 15-3; CA 125; Immunoassay; Tumormarker

Introduction

The great global burden of cancer diseases is mirrored by the 2012 report of the International Agency for Research on Cancer estimating 14 million cases of cancer diseases worldwide with over eight million cases of cancer-related deaths [1]. Much effort has gone into improving the diagnosis and therapy of cancer diseases, e.g. by qualified use of blood-based biomarkers, optimization of imaging techniques and identification of new “targeted cancer treatments”. In several types of cancer diseases, determination of tumor markers is recommended for diagnosis and therapy monitoring, for example [2, 3]. α-Fetoprotein (AFP) can be used in pre- and postoperative settings, e.g. in the prognosis and monitoring of liver cancer [4]. Hence, it can be applied as a screening marker in case of liver cirrhosis with high risk of developing hepatocellular carcinoma. In germ cell tumors, AFP is useful for diagnosis and monitoring [2]. Carcinoembryonic antigen (CEA) can be elevated in the serum of patients suffering from different solid tumors, such as colorectal, breast and lung cancers, and its diagnostic power lies in therapy monitoring, follow-up situations and early detection of recurrent disease [2, 4, 5]. Prostate-specific antigen (PSA) and free PSA (fPSA) play an important role in diagnosis and therapy monitoring in patients suffering from prostate cancer [2]. Using PSA as a screening marker for prostate cancer is still controversially discussed [6, 7]. While CA 15-3 is not recommended in screening situations, it is of prognostic power in cases of breast cancer in preoperative situations, in early detection of tumor recurrence and for therapy monitoring [2]. CA 19-9 is a hapten of the Lewis-a blood group determinant and therefore not expressed in Lewis-(a-b-) phenotype individuals [8]. It is the most important marker in follow-up situations of pancreatic cancer and can be elevated in other gastrointestinal malignancies, such as gastric, gall bladder or colorectal cancers [9]. CA 125 is of fundamental importance in ovarian tumors and is mainly expressed in the most frequent serous histological subtype [10]. It has to be noted that elevated levels of tumor markers can also be found in a series of benign diseases [11, 12].

All of the established guidelines recommend comparative measurements when changing methods for measuring tumor markers. Although luminescent oxygen channeling immunoassays (LOCI™)- based tumor marker assays had been introduced in daily laboratory routine several years ago, only limited data are available regarding method comparisons with immunoassays. In earlier studies, we compared chemiluminescence immunometric assays with LOCI™-based tumor marker assays for tumor markers AFP, CEA, CA 125, CA 15-3, CA 19-9, PSA and fPSA. Higher variations were detected for CA 19-9, CA 15-3, AFP, CEA and fPSA, and data for PSA and CA 125 showed good general correlations [13, 14]. Further studies reported on the analytical performance of CEA, AFP, CA 19-9, CA 125 and CA 15-3 using LOCI™ technology and compared single tumor marker methods with Abbott AxSym™ (AFP), Beckman Access™ (CEA) and ADVIA Centaur™ (CA 15-3, CA 19-9 and CA 125). High concordances were detected between these tumor marker assays [15]. To our knowledge, no comparison data have yet been published regarding method comparisons between homogenous LOCI™-based tumor marker assays for Dimension™ VISTA and the widely distributed heterogeneous tumor marker immunoassays for Cobas™ e411.

Materials and methods

Samples

Parallel tumor marker measurements were performed in a total of 1088 sera comprising n=171 AFP, n=156 CEA, n=154 CA 125, n=154 CA 15-3, n=151 CA 19-9, n=171 PSA and n=128 fPSA measurements. All samples were serum samples measured during routine diagnostics at the central laboratory of the University Clinics Bonn, Germany, as a part of clinical examinations. Internal and external quality control accuracy specifications were followed according to the guidelines of the German Federal Medical Society (RiliBÄK).

Methods

Measurements for AFP, CEA, CA125, CA 15-3, CA 19-9, PSA and fPSA were performed under routine conditions with the LOCI™-based tumor marker assays for Dimension™ VISTA 1500 (Siemens Healthcare Diagnostics, Eschborn, Germany) and with the electrochemiluminescence immunoassays (ECLIA) for Cobas™ e411 (Roche Diagnostics GmbH, Mannheim, Germany).

Dimension™ VISTA 1500:

LOCI™ technology is based on a chemiluminescence immunoassay. It uses chemibeads and sensibeads which contain a chemiluminescent and a photosensitizer dye. Together with the biotinylated antibody, sandwiches are generated and then the sensibeads are added. Next, immunocomplexes are formed and a chemiluminescent reaction is triggered at 680 nm. Final detection takes place at 612 nm.

Performance data

  • AFP: Limit of detection (LoD) 0.5 ng/mL, cut-off value 8.0 ng/mL, analytical measurement range 0.5–1000 ng/mL (without dilution). Intra-assay coefficients of variation: 1.9%, interassay coefficients of variation: 1.75%.

  • CEA: LoD 0.12 ng/mL, cut-off value 3.0 ng/mL and 5.0 ng/mL for non-smokers and smokers, analytical measurement range 0.2–1000 ng/mL (without dilution). Intra-assay coefficients of variation: 2.1%, interassay coefficients of variation: 1.42%.

  • CA 125: LoD 1.5 U/mL, cut-off value 35.0 ng/mL, analytical measurement range 1.5–1000 U/mL (without dilution). Intra-assay coefficients of variation: 2.5%, interassay coefficients of variation: 2.81%.

  • CA 15-3: LoD 1.0 U/mL, cut-off value 35.0 ng/mL, analytical measurement range: 1.0–300 U/mL (without dilution). Intra-assay coefficients of variation: 2.4%, interassay coefficients of variation: 2.73%.

  • CA 19-9: LoD 2.0 U/mL, cut-off value 37.0 ng/mL, analytical measurement range 0.2–1000 U/mL (without dilution). Intra-assay coefficients of variation: 5.1%, interassay coefficients of variation: 2.08%.

  • PSA: LoD 0.010 ng/mL, cut-off value 4.0 ng/mL, analytical measurement range 0.01–100 ng/mL (without dilution). Intra-assay coefficients of variation: 2.0%, interassay coefficients of variation: 1.52%.

  • fPSA: LoD 0.015 ng/mL, cut-off value 19% PSA, analytical measurement range 0.015–20 ng/mL (without dilution). Intra-assay coefficients of variation: 1.7 %, interassay coefficients of variation: 2.15%.

Cobas™ e411:

Tumor marker assays on Cobas™ e411 use electrochemiluminescence technology, which is based on a sandwich principle. Biotinylated antibodies and antigen-specific antibodies (marked with a ruthenium complex) build a sandwich complex. Streptavidin microparticles are added and finally, after specific reactions, a photomultiplier measures the chemiluminescent emission.

Performance data

  • AFP: LoD 0.61 ng/mL, cut-off value 7.0 ng/mL, analytical measurement range 0.5–1000 ng/mL (without dilution). Intra-assay coefficients of variation: 2.8%, interassay coefficients of variation: 3.4%.

  • CEA: LoD 0.20 ng/mL, cut-off value 5.0 ng/mL and 6.5 ng/mL for non-smokers and smokers, analytical measurement range 0.2–1000 ng/mL (without dilution). Intra-assay coefficients of variation: 2.5%, interassay coefficients of variation: 3.6%.

  • CA 125: LoD 1.2 U/mL, cut-off value 35.0 U/mL, analytical measurement range 0.6–5000 U/mL (without dilution). Intra-assay coefficients of variation: 1.0%, interassay coefficients of variation: 2.5%.

  • CA 15-3: LoD 1.0 U/mL, cut-off value 26.4 U/mL, analytical measurement range 1.0–300 U/mL (without dilution). Intra-assay coefficients of variation: 2.5%, interassay coefficients of variation: 3.6%.

  • CA 19-9: LoD 0.6 U/mL, cut-off value 27.0 U/mL, analytical measurement range 0.6–1000 U/mL (without dilution). Intra-assay coefficients of variation: 4.4%, interassay coefficients of variation: 4.8%.

  • PSA: LoD 0.011 ng/mL, cut-off value 4.0 ng/mL, analytical measurement range 0.002–100 ng/mL (without dilution). Intra-assay coefficients of variation: 2.5 %, interassay coefficients of variation: 2.7%.

  • fPSA: LoD 0.01 ng/mL, a cut-off of 19% fPSA results in the detection of 90.2 % prostate cancers and avoids unnecessary biopsy in 17.6% of men without prostate cancer (fPSA/tPSA ratio in men with tPSA between 4 and 10 ng/mL tPSA), analytical measurement range 0.01–50 ng/mL (without dilution). Intra-assay coefficients of variation: 1.1%, interassay coefficients of variation: 3.5%.

Statistics

Descriptive statistics for the data are presented in Table 1. The D’Agostino-Pearsontest fornormaldistribution showed that data are not normally distributed. For method comparison, Spearman´s correlation coefficients were calculated. Bland-Altman plots were calculated and Passing-Bablok regressions analyses were performed (Medcalc®, Version 11.0.0.0).

Table 1:

Value distribution for AFP, CEA, CA 125, CA 15-3, CA 19-9, PSA, PSA<4 ng/mL and fPSA.

nMedianMin.25%75%Max.
AFP_Cobas, ng/mL17411.10.55.757.236099.0
AFP_VISTA, ng/mL17411.90.75.762.435587.7
CEA_Cobas, ng/mL1569.50.24.878.512460.0
CEA_VISTA, ng/mL1568.10.53.877.420912.5
CA 125_Cobas, U/mL15460.86.424.6142.510492.0
CA 125_VISTA, U/mL15446.53.820.393.18269.2
CA 15-3_Cobas, U/mL15455.35.122.098.24814.0
CA 15-3_VISTA, U/mL15442.33.017.777.42042.6
CA 19-9_Cobas, U/mL15148.40.619.4142.618020.0
CA 19-9_VISTA, U/mL15145.82.011.0258.444653.6
PSA_Cobas, ng/mL17111.1<0.0024.5247.63824.0
PSA_VISTA, ng/mL17110.6<0.014.5273.8>10000.0
PSA_Cobas, ng/mL400.8<0.0020.31.11.9
<4 ng/mL
PSA_VISTA, ng/mL400.8<0.010.31.21.9
<4 ng/mL
fPSA_Cobas, ng/mL1560.90.20.61.314.0
fPSA_VISTA, ng/mL1280.60.10.40.92.6

n, median, minimum (min.), 25th percentile, 75th percentile and maximum (max.) are listed for AFP AFP, CEA, CA 125, CA 15-3, CA 19-9, PSA, PSA<4ng/mL and fPSA.

Results

Comparison of the Dimension™ VISTA assays and the Cobas™ e411 assays yielded high correlation coefficients for AFP (R=0.994; p<0.0001), CEA (R=0.993; p<0.0001) and PSA (R=0.999; p<0.0001). In addition, only minor slopes and intercepts were found for AFP (slope 1.03; intercept +0.25), CEA (slope 0.94; intercept −0.07) and PSA (slope 1.05; intercept −0.01), underlining the excellent comparability of these parameters with both methods. It has to be pointed out that for the clinically meaningful range of PSA <4 ng/mL, both methods correlated very well (R=0.973; p=0.0003; slope 1.00; intercept +0.01) (Figure 1 ).

Figure 1: Passing-Bablok regression analysis for total and lower ranges of AFP, CEA, CA 125, CA 15-3, CA 19-9, PSA, fPSA and PSA<4 ng/mL.Displayed are Passing-Bablok regression analyses and regression equations for total and lower ranges of AFP, CEA, CA 125, CA 15-3, CA 19-9, PSA, fPSA and PSA<4 ng/mL. Tumor markers were measured with assays for Dimension™ VISTA 1500 and Cobas™ e411. (A) CEA ng/mL. (B) CEA up to 50 ng/mL. (C) AFP ng/mL. (D) AFP up to 200 ng/mL. (E) CA 15-3 U/mL. (F) CA 15-3 up to 200 U/mL. (G) CA 125 U/mL. (H) CA 125 up to 200 U/mL. (I) CA 19-9 U/mL. (J) CA 19-9 up to 200 U/mL. (K) PSA ng/mL. (L) PSA up to 20 ng/mL. (M) PSA<4ng/mL. (N) fPSA ng/mL.
Figure 1:

Passing-Bablok regression analysis for total and lower ranges of AFP, CEA, CA 125, CA 15-3, CA 19-9, PSA, fPSA and PSA<4 ng/mL.

Displayed are Passing-Bablok regression analyses and regression equations for total and lower ranges of AFP, CEA, CA 125, CA 15-3, CA 19-9, PSA, fPSA and PSA<4 ng/mL. Tumor markers were measured with assays for Dimension™ VISTA 1500 and Cobas™ e411. (A) CEA ng/mL. (B) CEA up to 50 ng/mL. (C) AFP ng/mL. (D) AFP up to 200 ng/mL. (E) CA 15-3 U/mL. (F) CA 15-3 up to 200 U/mL. (G) CA 125 U/mL. (H) CA 125 up to 200 U/mL. (I) CA 19-9 U/mL. (J) CA 19-9 up to 200 U/mL. (K) PSA ng/mL. (L) PSA up to 20 ng/mL. (M) PSA<4ng/mL. (N) fPSA ng/mL.

However, correlations of both platforms were only moderate for CA 125 (R=0.976), CA 19-9 (R=0.960), fPSA (R=0.950) and CA 15-3 (R=0.940). In addition, considerable slopes were observed for these markers such as for CA 125 (slope 0.64; intercept +1.91), CA 19-9 (slope 1.50; intercept −12.61), CA 15-3 (slope 0.76; intercept −0.73) and fPSA (slope 0.75; intercept +0.01) (Figure 1). Bland-Altman plots for all comparisons are shown in Figure 2 .

Figure 2: Bland-Altman plots for AFP, CEA, CA 125, CA 15-3, CA 19-9, PSA, fPSA and PSA<4 ng/mL.Displayed are Bland-Altman plots for AFP, CEA, CA 125, CA 15-3, CA 19-9, PSA, fPSA and PSA<4 ng/mL depicting the difference between the tumor marker values and plotted against the mean value of both measurements. The mean line shows the mean difference of the measurement values. The SD (standard deviation) lines represent the limits of agreement within which 95% of differences between measurements by the two methods are expected to lie. Tumor markers were measured with assays for Dimension™ VISTA 1500 and Cobas™ e411. (A) AFP. (B) CEA. (C) CA 125. (D) CA 15-3. (E) CA 19-9. (F) PSA. (G) fPSA. (H) PSA<4ng/mL.
Figure 2:

Bland-Altman plots for AFP, CEA, CA 125, CA 15-3, CA 19-9, PSA, fPSA and PSA<4 ng/mL.

Displayed are Bland-Altman plots for AFP, CEA, CA 125, CA 15-3, CA 19-9, PSA, fPSA and PSA<4 ng/mL depicting the difference between the tumor marker values and plotted against the mean value of both measurements. The mean line shows the mean difference of the measurement values. The SD (standard deviation) lines represent the limits of agreement within which 95% of differences between measurements by the two methods are expected to lie. Tumor markers were measured with assays for Dimension™ VISTA 1500 and Cobas™ e411. (A) AFP. (B) CEA. (C) CA 125. (D) CA 15-3. (E) CA 19-9. (F) PSA. (G) fPSA. (H) PSA<4ng/mL.

While for AFP, CEA and PSA only 35, 92 and 17 samples showed discrepancies of more than 20% between both methods, numbers were considerably higher for CA 125 (n=114), CA 19-9 (n=104), CA 15-3 (n=116) and fPSA (n=93). Discrepancies of more than 25% between both methods were 9% for AFP, 42% for CEA, 5% for PSA, 64% for CA 125, 61% for CA 19-9, 59% for CA 15-3 and 47% for fPSA. Special attention has to be drawn to the ratios of free to total PSA, as this criterion is used for clinical decision making. As Dimension™ VISTA assays measure considerably lower concentrations of fPSA but comparable concentrations of total PSA than the Cobas™ e411 assays, the ratios will be only 75% in the average, which makes an adjustment of interpretation ranges necessary. As differences in single patients may be clinically relevant, marker courses can only be interpreted when the same method is applied. Further, it underlines the necessity of parallel assessments with both methods when platforms are changed in a laboratory.

Discussion

In the present study, we examined the comparability of the homogenous LOCI™-based tumor marker assays for Dimension™ VISTA and tumor marker immunoassays for Cobas™ e411 for AFP, CEA, CA 125, CA 15-3, CA 19-9, PSA and fPSA. Inter- and intra-coefficients of variability (CV) showed good comparability. Both CVs according to the manufacturer’s instructions as well as our CVs under routine conditions were comparable. Reaction times varied between the different manufacturers, i.e. the electrochemiluminescent reaction time is 18 minutes, while the LOCI reaction time is 10–21 minutes (CA 125) according to the manufacturer´s instructions. Regarding tumor marker measurements, the main problem for laboratory diagnostics is the lack of a reference method except for AFP, PSA and fPSA. Therefore, comparability of most available assays has to be determined by parallel measurements. When a method is changed, attention must focus on tumor marker results. In our study, we demonstrated an excellent correlation and similar values in the assays for AFP, CEA, PSA and PSA (<4 ng/mL). This is probably due to the fact that an international standard exists for AFP and PSA (AFP: WHO Standard 72/225) [16]. A comparison between the tumor marker assays is difficult due to assay-specific antibodies. Both assay technologies work with monoclonal mouse antibodies but specific information about the exact epitope binding sites is missing. Measurement methods are also different. The Cobas™ e411 assay is based on electrochemiluminescent technology while the Dimension™ VISTA assay is based on LOCI™ technology. Moreover, standardization (if available) also differs. For example, the Cobas™ e411 assay for CEA is based on a single step sandwich technology, working with a biotinyl and a ruthenyl mouse antibody, which bind at two different CEA epitopes. The CEA method is traceable on IRP WHO 73/901. However, while the manufacturer’s instruction for the Dimension™ VISTA assay for CEA provides information about monoclonal antibodies, there is no information on standardization.

Correlations were weaker for CA 125, CA 15-3 and fPSA, despite the fact that there is an international standard for fPSA (WHO Standard 96/668). For CA 19-9, a good correlation was shown, whereas slope and intercept revealed only moderate performance. Therefore, for CA 125, CA 15-3, fPSA and CA 19-9, the reported slopes have to be considered when changing methods for assessment of these tumor markers in a laboratory. Generally, other studies also showed that method comparisons for these markers are difficult and values cannot be easily compared [17, 18]. In ring trials, Youden plots generated by the Reference Institute for Bioanalytics (RFB) revealed varying results with a great CV span, but generally, the cohorts for the different assays performed well.

In accordance with the guidelines that thorough comparisons should be performed due to the variability of the available tumor marker assays in daily laboratory diagnostics, we demonstrated the analytical performance of the LOCI™-based tumor marker assays for Dimension™ VISTA [19]. In contrast to the other immunoassays, LOCI™ technology omits one washing step. While this could lead to the assumption of a disadvantage regarding sensitivity, our study showed that this was not the case for CEA, AFP and PSA.

Other method comparisons between LOCI™-based tumor marker assays and tumor marker assays for Immulite 2000 XPI revealed, in general, a good correlation, but especially for CA 19-9 and CA 15-3, significant differences were reported [13, 14]. When comparing tumor marker methods based on LOCI™ technology and Abbott AxSym® (AFP), Beckman Access® (CEA) and ADVIA Centaur® assays, high concordances were detected [15]. Further studies compared the analytical performances of LOCI™-based assays for cardiac troponin I and for N-terminal pro-B-type natriuretic protein with Siemens Immulite 2500 and Siemens Dimension EXL [20, 21]. In general, we can conclude that for the different methods used under routine diagnostic conditions, limitations and analytical challenges exist. It is, therefore, of crucial importance to report results of method comparisons under routine conditions. In our study, a large panel of sera was investigated and levels were determined over the entire analytical range. In the case of PSA, the clinically relevant cut-off <4 ng/mL was further investigated and the results showed an excellent correlation. Nevertheless, in individual patients, differences in values were observed. This emphasizes the importance and necessity of performing parallel measurements when changing methods. Due to methodological discrepancies, it is of importance to closely collaborate with clinicians, while individualized evaluation of the received results should be carefully conducted. To date, harmonization of immunoassays regarding tumor marker determination is still missing [22].

In the present study, the focus was on method comparison. In a next step, the clinical performance of these tumor marker assays will be tested with a specific focus on the verification of clinical validity and diagnostic interpretation ranges.

Conclusions

In this study, results are presented for the first time regarding method comparisons for tumor marker levels of AFP, CEA, CA125, CA 15-3, CA 19-9, PSA and fPSA comparing the LOCI™-based tumor marker assays for Dimension™ VISTA 1500 with the electrochemiluminescence assays for Cobas™ e411. We found strong correlations for AFP, CEA and PSA. Correlations were weaker for CA125, CA15-3, fPSA and CA 19-9. For these tumor markers, the reported slopes must be considered when changing measurement methods for tumor marker determination in a laboratory. Clinical performances are still rare and further investigations are required. In accordance with existing guidelines, our study stresses the importance of parallel measurements for an appropriate time period when changing measurement methods for the detection of tumor marker levels.

Corresponding author: Ramona C. Dolscheid-Pommerich, MD, Department of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, Sigmund- Freud- Str. 25, 53127 Bonn, Germany, Phone: +49 228 287 12180, Fax: +49 228 287 12159

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: Reagents were provided by Siemens Healthcare Diagnostics.

  3. Employment or leadership: None declared.

  4. Honorarium: SH and RDP received honoraria for lectures by Roche Diagnostics, Siemens Healthcare Diagnostics and different companies.

  5. Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

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Received: 2016-10-18
Accepted: 2016-12-4
Published Online: 2017-1-31
Published in Print: 2017-2-1

©2017 Walter de Gruyter GmbH, Berlin/Boston

This article is distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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  2. Editorial
  3. Laboratoriumsmedizin oder Journal of Laboratory Medicine – Gedanken zur zukünftigen strategischen Ausrichtung
  4. Onkologie/Oncology
  5. Method comparison of tumor markers assessed by LOCI™- and ECLIA-based technologies
  6. Endokrinologie/Endocrinology
  7. Der Einfluss von Geschlecht, Body-Mass-Index und Alter auf das Ergebnis des 2 mg Dexamethason-Kurzzeit-Suppressionstestes
  8. Originalarbeiten/Original Articles
  9. Der zlog-Wert als Basis für die Standardisierung von Laborwerten
  10. Expression of connexin 32 and connexin 43 in the cerebral cortex of patients with refractory epilepsy
  11. Overexpression of interferon-γ and indoleamine 2, 3-dioxygenase in systemic lupus erythematosus: relationship with the disease activity
  12. Kurzmitteilung/Short Communication
  13. Red blood cell morphology in patients with β-thalassemia minor
  14. Arbeitsgruppenbericht/Working Group Report
  15. Festlegung der zulässigen Messunsicherheit quantitativer Messgrößen in der Laboratoriumsmedizin
https://doi.org/10.1515/labmed-2016-0074
Keywords for this article
AFP; CA 15-3; CA 125; immunoassay; tumor marker
Creative Commons
BY-NC-ND 3.0

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. Laboratoriumsmedizin oder Journal of Laboratory Medicine – Gedanken zur zukünftigen strategischen Ausrichtung
  4. Onkologie/Oncology
  5. Method comparison of tumor markers assessed by LOCI™- and ECLIA-based technologies
  6. Endokrinologie/Endocrinology
  7. Der Einfluss von Geschlecht, Body-Mass-Index und Alter auf das Ergebnis des 2 mg Dexamethason-Kurzzeit-Suppressionstestes
  8. Originalarbeiten/Original Articles
  9. Der zlog-Wert als Basis für die Standardisierung von Laborwerten
  10. Expression of connexin 32 and connexin 43 in the cerebral cortex of patients with refractory epilepsy
  11. Overexpression of interferon-γ and indoleamine 2, 3-dioxygenase in systemic lupus erythematosus: relationship with the disease activity
  12. Kurzmitteilung/Short Communication
  13. Red blood cell morphology in patients with β-thalassemia minor
  14. Arbeitsgruppenbericht/Working Group Report
  15. Festlegung der zulässigen Messunsicherheit quantitativer Messgrößen in der Laboratoriumsmedizin
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